E43 - Survey Says: Migraines want Canna-bliss

If you suffer from headaches, Dr. Carrie Cuttler, Assistant Professor at Washington State University, may offer some insights. This episode explores how migraine sufferers may benefit from cannabis. In her study, this cannabis researcher, uses Strainprint data to track people who use inhale cannabis to treat their migraines. Kirk and Trevor explore her research and also discuss how diminished anandamide levels, an important endocannabinoid, may also contribute to the headache pain.  A deficiency in the `bliss` molecular causes a pain in the ...head? 

This Episode is sponsored by Strainprint

Saturday, 11 January 2020 21:36

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Episode Transcript

Trevor: So, Kirk, we're back in studio.

Kirk: Hey, Trevor how's it going?

Trevor: Good. We just talked to a really interesting lady from Washington State about some well, first, she stressed us out by talking about an unrelated stress study she did on cannabis users, but she was talking about migraines.

Kirk: Yes. Dr. Carrie Cuttler, Ph.D., that's where a doctor comes from. She is an associate professor Washington State University with the Department of Human Development (Error – Department of Psychology). And she is a cannabis researcher. And you found her you found it through Twitter?

Trevor: No, actually found through all good things we found or through Strainprint.

Kirk: Oh, OK. We should actually declare this upfront. This study was you was  a review of Strainprint data,.

Trevor: All using Strainprint data.

Kirk: And we are fans of Strainprint. So, I'm going to declare that this is a Strainprint positive episode just by the fact that the study was used Strainprint.

Trevor: Absolutely.

Kirk: OK, and not the fact that Strainprint sponsors a lot of our episodes. That's so.

Trevor: Yeah, unrelated.

Kirk: Unrelated. So I am. Kirk Nyquist the nurse. This is Reefer Medness - The podcast.

Trevor: I'm Trevor Shewfelt. I'm the pharmacist.

Kirk: And we are going to talk to Dr. Carrie Cuttler. Short and long term effects of cannabis on headaches and migraines.

Dr. Cuttler: My name is Dr. Carrie Cuttler. I have a Ph.D. in psychology and I work as an assistant professor in the Department of Psychology at Washington State University.

Kirk: So, Trevor, this is a qualified researcher we have here.

Trevor: Yes. Sounds like eminently qualified, has been doing a lot of stuff with cannabis. And like she said, both in the lab where she put people through ridiculous amounts of stress of watching them subtract seventeen. Well, sticking their heads in cold water while watching a video of themselves to see how stressed they were or weren't. That sounds terrifying. And then she's done other studies with we'll call it epidemiological, where she's taking numbers from Strainprint like so there's no patients in the lab, no participants in the lab. But she's got anonymized participants through the Strainprint app and sort of she put some people in the group. Like she said, she you were in the study group if you're using inhaled cannabis, you're out of the study group if you're using oral, like, orally consumed. You're in the study group if you report to your migraine up front and then saw whether or not you said if your migraine got better or worse within twenty minutes to four hours. You were out of the study group if you didn't report back. So, she sort of took the data from Strainprint. But still the subgroup she got out of there of sort of usable data was still pretty huge.

Kirk: Yeah. Twenty thousand hits. And the other thing that they did Strainprint provided them the codes for the users. So, they're so if you are user zero zero one one zero, they could follow how many times zero zero one one zero. How many times they used it so they could track that individuals several times.

Trevor: Over time.

Kirk: Over time.

Trevor: So you could see things like and she gets into it later on, tolerance like do you now need more cannabis to treat your migraine than you did six months ago?

Kirk: Yeah, the highlights of the study they found is that headaches and migraine ratings were reduced by up to 50 percent.

Trevor: Yeah, that's a big number.

Kirk: That's a huge. No men reported larger reductions of headaches after cannabis in women. But you know what I find that I find, what is it, one percent difference between the sexes. So although they reported more men, but I don't know if that's huge.

Trevor: She called it statistically significant, but.

Kirk: Only one percent.

Trevor: Yeah, but it's everything about a migraine study is hard because it's not like a blood pressure study where we can put a cuff on someone to measure what actually happened to the blood pressure.  Everything migraine related, whatever study you do has to be sort of self reporting of how did your numbers get on a scale from one to ten? How bad is your headache? So it's all a little mushy.

Kirk: Well, we've talked about the pain scale in the past, and the pain scale is something that came out in the 80s that basically bit the opioid industry in the butt afterwards. But the pain scale is: tell us what your pain is now and tell us what your pain is after we give you an intervention. That's how the pain scale is supposed to work. When someone says that their pain is ten, that means nothing until you have done something to alleviate the pain, then the pain scale becomes relevant. Right. Because you're taking the subject of pain value that someone gives, you do an intervention. Now tell us. So that's how the pain scale works. Another highlight of the study is that cannabis concentrates more related to larger reduction in. Headaches than flower, although she does say that there is not a lot of concentrate data in the overall stud.  Evidence for tolerance of effects of cannabis on headaches and migraines was detected and evidence for medication overuse headaches was also not detected. Those two points I found very fascinating. You brought those forward.

Trevor: Yeah, and we'll talk about this more with her. But people don't think about it. But you can get headaches from using your headache medication. And the one I always think of because it was completely unrelated to headache. It was young, a woman who had a child by C-section, which is, you know, it's an operation. So, it's painful. And so she was using indomethacin suppositories. A normal thing to do. And, you know, she kept getting these headaches and these headaches weren't going away. And it took a while to figure out, well, she was using too much of the indomethacin suppository and that was giving her headaches and, you know, weaned her off of the indomethacin suppository and the headaches went away. So, using too much of the pain medication can give you these medication overuse headaches.

Kirk: I've seen that in people that use narcotics, people that are using hydromorphone or people using Tylenol 3 for a long period of times. I have seen that. Whereas you cut them off of those meds, cold turkey is not a great idea, but all of a sudden that headache is gone.

Trevor: Yeah. Let's listen to Dr. Cuttler. This is a good one.

Kirk: Maybe introduce the research that you've done.

Dr. Cuttler: Sure. In my Health and Cognition Lab, I focus on examining the acute, as well as the chronic effects of cannabis on cognition, emotion, and mood. And in this study, I examined the acute effects of cannabis on headache and the migraine. And that's because a lot of people report using cannabis for headache and migraine and they claim that they find that it's effective in reducing their symptoms. However, there's been surprisingly few studies that have actually examined the effectiveness of cannabis, particularly whole plant cannabis on headache and migraine. To my knowledge, there's only been one previous study. It was a clinical trial, sorry, only one clinical trial that's examined the effectiveness of a drug called Nabilone on headache. And they found that this drug was more effective than ibuprofen and reducing pain and increasing quality of life. But this is a synthetic cannabinoid. And again, very few studies have ever looked at the effects of whole plant cannabis. And so we wanted to fill that gap in the literature.

Kirk: So you are a cannabis researcher, so you spend a fair bit of your day looking at cannabis?

Dr. Cuttler: Yes, yes. Studying cannabis, yes.

Kirk: So as an introduction to yourself, give us just an overview of other research you've done on cannabis before we focus on the study.

Dr. Cuttler: Sure. You've done a large number of studies. I've done research looking at the effects of cannabis on stress, both the chronic and acute effects. So looking at acute effects, we found that inhaled cannabis reduced perceived stress by almost 60 percent. And in another study, we actually had cannabis users and nonusers and we subjected half of them to a fairly severe stressor. For the stressor they had to put their hand in ice cold water for intermittent periods of time that were unpredictable to them. In between putting their hand in ice water, they had to count backwards from two thousand forty-three by Seventeen's, and every time they made a mistake, they were told that they needed to start again. And there was a webcam directed at them and it was projecting their image back to them. So, they had to watch themselves undergo this stressor.

Kirk: I wonder how they sober people did with that?

Dr. Cuttler: Yes, they were all they were all sober. We had cannabis users and non-users, and then the other half of them went through a no stress manipulation. So that no stress, they just had to put their hand to tip their hand and lukewarm water and count from one to twenty-five. And there was no video recording or anything like that. And we looked at cortisol and subjective stress ratings and we measured days before and after the stressor. And we looked at changes in cortisol and changes in stress ratings from before to after the stressor. And what we found was what you would expect in nonusers and that nonusers reported higher levels of stress after the stress manipulation and their cortisol, which is a stress hormone, increased after the stress manipulation. In contrast to cannabis users in the stress and no stress condition. So, the same changes in cortisol. So, we saw what we called a blunted stress response in cannabis users and that their cortisol, the stress hormone, really just did not increase like the nonusers did. And they also reported smaller increases in subjective stress than the non-cannabis users. So, this suggests that cannabis acutely diminishes stress. The first study showed that. And then in this second study, we are finding basically that these stress relieving properties of cannabis seem to be extending beyond the period of intoxication. And people are reporting less of a stress response in response to a stress challenge.

Kirk: You are obviously a knowledgeable person. You've done credible research on cannabis. Can you give us a summary of the research and then I'll get into specific points?

Dr. Cuttler: Sure. So, what we did for this study, because it's very hard to examine the acute effects of cannabis, especially in the United States, where cannabis is considered a Schedule One drug, which means that it's believed to have a high risk of abuse and dependence and no medical benefits. And with that scheduling of cannabis, it makes it very, very hard for researchers to get access to the drug and to administer it to participants. And so, what we did was we worked around these laws a little bit by examining archival data from this medical marijuana app called Strainprint. And so, using this app, medical cannabis patients can actually rate their symptoms of a whole bunch of different conditions immediately before and after using cannabis. And so, we looked at over thirteen hundred medical cannabis patients who use the app over 12,000 times to track their changes in headache from immediately before to after cannabis use. And we looked at over 600 medical cannabis patients who use the app over 7,000 times to track changes in migraine from before to after using cannabis. And we found that both headache and migraine severity ratings were reduced by about 50% from before to after cannabis use. We also looked at things like the type of cannabis people were using. So, were they using flower or concentrates? We looked at gender and dose and THC and CBD levels, and what we found was that cannabis concentrates were actually associated with larger reductions and headache severity ratings relative to more traditional flower. Although the flower was also associated with significant reductions in headache ratings. And we found that males reported greater headache relief than did females, although females still reported significant relief of headaches as well.

Kirk: All right. That's cool. Now, just up front for the people that like to read research now, they're the conflict of interest. There is no conflict of interest in this study. Nobody was paid for this study. Nobody has a interest in any of the study.

Dr. Cuttler: No. No, I don't have any ties to the medical cannabis community. I'm paid by Washington State University solely.

Kirk: Okay.

Dr. Cuttler: Strainprint provided the data to me free-of-charge. They are interested in medical cannabis science and so they're supportive of the scientific community. They had no say in the analysis or the results or the findings or what we published. What they did do, however, was pay for the open access fee for the journal. And that's just so that the paper could be freely available to everyone, rather than just limited to the scientific community.

Kirk: Oh, this is important to get research out.  In Canada and you're a Canadian, so you're so you're fully aware that Canada is now legal so research and can happen. So I'm expecting you to, you know, come to Canadian University and start doing some research here. Is that any plan?

Dr. Cuttler: Oh, yes. If they would bring me, I'm at an American university because of a difficulty in finding jobs in Canada at this time. So, there's just a lot more universities in America to find work at. And I was never successful in getting a position at a Canadian university, but I sure would love to come home someday.

Kirk: Well, we'll put it out to all the academics that listen to our podcast. I'm looking at this research again. Now, can you explain to me a little bit about anandamide and deficiency that we find with people with headaches, and the endocannabinoid system?

Dr. Cuttler: Yeah. So, there is some evidence that they may have lower levels of anandamide. Now anandamide is basically an endocannabinoid as opposed to a Phyto-cannabinoids. So, we would find Phyto-cannabinoids in the cannabis plant. Examples would be THC and CBD are Phyto-cannabinoids. But we also have endocannabinoids.  These are basically endogenous cannabinoids, meaning that our body. And brain produces these cannabinoids naturally and in some pleasurable activities and substances, will also boost the endocannabinoid system. For instance, running will boost the endocannabinoid system. People used to think that the runner's high was like a euphoria produced more by the opioid system. We now know that the endocannabinoid system plays a role in that as well. Chocolate can activate the system.  So, things that basically make us feel good activate this system. And the system is also believed to help to protect us against things like depression, and it helps with the recovery of the stress response. And so, if people are deficient in anandamide, and that might make them more susceptible to things like depression and anxiety, but in this case, also potentially headaches. And so artificially activating the system using drugs like cannabis could also help patients, as is the it's the theory.

Kirk: Looking at the actual methodology. So, you use Strainprint. So how did that work? So how did you draw the data from Strainprint?

Dr. Cuttler: Basically, the folks that Strainprint pulled the data for me and sent it to me in an entirely anonymous forum so that I would not know who anybody is and would have no way of knowing who any individual is in the data set. They sent me data again on nearly 2,000 patients who had used the app collectively almost 20,000 times. So, we are looking at change in headache and migraine from before to after about 20,000 cannabis use sessions. So very big data, very different from any typical study that you find in the scientific community, and especially very different from any clinical trial where, you know, people are usually looking at 30, 50, maybe 100 patients or individuals. Here, we're looking at over 2,000 and we're looking at over 20,000 cannabis use sessions.

Kirk: And this is actually a new study. Right? There's no other studies like this in the literature right now.

Dr. Cuttler: No. There are studies looking at effects of cannabinoids and cannabis on headache and migraine. But most of those studies used either a retrospective reporting or they again, used synthetic cannabinoids like Nabilone rather than whole plant cannabis. And what I mean by retrospective studies is that they basically just ask people, you know, how does cannabis help with your headaches? You know, are your headaches reduced when you use cannabis? And so just asking them to think back to the times that they had used cannabis in the past and whether they found it helpful or not, and how much they perceive that it reduced their symptoms. And we just worry about that type of research. I mean, it gives us a nice insight, but it could be biased by sort of retrospective reporting. People might have memory biases at play. They might be trying to overestimate the effects of cannabis in order to sort of shed a good light on cannabis and justify their use of it. So, using the app data is better because, well, we have large data, which is always beneficial. It makes the results more generalizable, but also looking at their ratings immediately before and after. We don't worry about any sort of retrospective recall biases or anything like that. Also, the people who are using this Strainprint app are using it for their own personal reasons. So, people are using this app to get a better sense of which strains and which doses are helping them personally the most. And that's sort of the motivation for using the app, is that there's so many different strains out there. People can be a little bit overwhelmed on knowing which strains are going to help them personally the most. And so, the app helps them to track that themselves so that they can figure out what strains and doses are benefiting them the most. And they're not really aware necessarily that the data are being used for scientific reasons. And so, we remove any possibility that people are sort of overestimating the effects because they're really just tracking this for personal reasons. Now, in the terms of use on this Strainprint app, it does indicate that Strainprint has the right to use the data in any way they see fit. And once again, we'd get anonymous data and we go through the Office of Research Assurances to make sure that we are meeting all ethical standards in obtaining and analyzing those data as well.

Kirk: Okay, so using Strainprint and we're familiar with Strainprint in this podcast, somebody self-administered their cannabis. And they declare in Strainprint that my headache is a seven today. I inhale. Now, this study was inhaled cannabis, right? There is no. So it's inhaled cannabis. So now, 20 minutes later, was this constant in all of the all of the participants. Twenty minutes later, they go back to the Strainprint app and now they see my headache is now a two, for example.

Dr. Cuttler: So basically, they receive a push notification 20 minutes after the initial symptom rating, the idea being that they're going to use cannabis in those 20 minutes and then come back and report how they feel after using cannabis. But they don't have to report within 20 minutes exactly.  What we did was we limited responses between 20 minutes and four hours. And that's because we know that the acute effects of cannabis are not going to persist beyond four hours. So we didn't want to include anyone who had rated, rerated their symptoms, you know, more than four hours after cannabis use. But not everybody rates right at the 20-minute mark. Some people wait an hour, some people wait a couple of hours. And so, we didn't want to lose all of that information as well. So, anybody who rerated between 20 minutes and four hours was included in the analysis. You're right that we only we only included inhaled cannabis sessions. And that's because, again, we understand the period of intoxication better for inhaled cannabis. We know the effects are fairly immediate and we know they're not going to persist beyond four hours, whereas oral administration tinctures, that type of thing, it can be a lot harder to capture the period of intoxication because different people have different sort of onset periods for the effects of the drug. And it can last for variable amounts of time depending on the individual. And so, it it's just harder to capture the period of intoxication for oral administrations and other methods of administration. So, for this study, we only focused on inhaled cannabis.

Kirk: Okay. Now the fact is Strainprint is a self-populating tool in that it's it takes subjective information and objectifies it. You’ve taken that information out. Is there any flaws in that methodology of research if someone is putting subjective information into an objective tool?

Dr. Cuttler: Well, I mean, we have to sort of trust that people are accurately reporting things. But we also know that not everybody does accurately report everything. So people might be a little bit inaccurate in the doses they report. For instance, people might be inaccurate in the THC and CBD information that they input into Strainprint. Because we were concerned about that. We only included sessions for which the THC and CBD content for the cannabis used was pulled from a Canadian producer’s website because we thought that that would be a bit more objective than trusting people's self-reports about the THC and CBD content in the cannabis. Now while we trust the THC and CBD content that's posted on the Web sites for these various producers, a lot more than we might necessarily completely trust user input of information. We also know that the testing of the THC and CBD content is not terribly reliable and that can be quite variable. So the same strain per-say, different products from the same strain might actually have different THC and CBD levels just because of variability in testing and batches and things like that. So the fact that we didn't find any evidence that THC or CBD or interactions between THC and CBD predicted any changes in headache or migraine, we're not sure if that's because THC and CBD don't actually matter, that various doses of THC in CBD are equally effective. It could also just mean that the THC and CBD information that we had is not terribly reliable.

Kirk: OK, thanks. Thank you for mentioning that because I did want to explore that component of the plant medicine. One of the difficulties of plant medicine is the consistency of the ingredients that you're getting. So thank you for raising it. And I did notice in the study that that is actually taken in consideration. What you found is it didn't matter the strain. It didn't matter the percentage of cannabinoids in the flower. What you discovered is that someone that uses cannabis for a headache does get positive results. And that's sort of the end statement.

Dr. Cuttler: Yes, flower, concentrates, any dose and any THC and CBD content. None of that seemed to matter. All of it was associated with significant reductions in headache and migraine.  As I mentioned earlier, the cannabis concentrates, those that were associated with larger reductions in cannabis flower, but cannabis flower also produced significant reductions.

Kirk: And I read that and I wondered if that actually doesn't validate your study a little bit more. And I say this because when you look at the Nabilone results, Nabilone is a synthetic cannabinoid, therefore, there's no entourage effect. When you're smoking concentrate you definitely have a concentrate of a THC level or a CBD level. Are the other components and I don't know the answer to this question. It's a question I am throwing out there and I'm not sure if you know it either. Are the other components? Is the entourage effect in effect with concentrates?

Dr. Cuttler: I think that it can be, yes, because the concentrates are not just pure THC. The concentrates have various other cannabinoids re-added back basically into the concentrate. And terpene can also be presentence in these concentrates.

Kirk: I guess it’s the quality of the producer.

Dr. Cuttler: Yeah, yeah. So, we and we didn't have information on all of the more minor Phyto-cannabinoid things like CBG and CBC and CBN. We didn't have enough data on those minor cannabinoids and we didn't have enough data on Terpenes to consider those in any of these analyzes. And so, it could be some of the more minor Phyto-cannabinoids. It could be Terpenes, as you said, it could be an entourage effect of just, you know, the various combinations of all of these different constituents. Again, we're not sure what it is that's producing the effect. Now, one thing I have wondered for a long time about the effects of cannabis on pain and that I personally think is what's happening. As a psychologist who studies the effects of cannabis on mood and emotion and stress, I think that what might be happening is that cannabis might not necessarily affect the pain directly, so much as indirectly by affecting the emotional response to pain. I personally think that people simply are less distressed by the pain. They are less upset about the pain, and they're able to emotionally, potentially distance themselves from the pain somewhat. So, that the pain might sort of be there in the background. But it's not so much bothersome to them anymore. This is pure speculation on my part, but it's something that I've always thought was one mechanism by which cannabis might actually be reducing pain. It's just reducing people's distress about the pain.

Kirk: And I think I can agree with that because you just sort of describe somebody who after enjoying a bowl of flower, they tend to lay back and yeah, their stress levels is notably different. Focusing on tolerance. Part of your study talked about tolerance. And can you speak a little bit about that?

Dr. Cuttler: Sure, I can, yes. So, one thing that we examined was evidence for tolerance to the effects. And we did this in a couple of different ways. One way we looked at it was just looking at whether people's dose of cannabis increased across time. So, one thing to keep in mind with these data are that we're actually able to look at the same individuals across a fairly lengthy period of time and look at the amount of cannabis that the individuals are using over time. And what we found was small but steady increases in the amount of cannabis that people were using to manage their headaches and migraines. We looked at dose or quantity by looking at the number of Puff's people were taking, and we just found a significant increase in the number of puffs across time, which makes sense. I mean, we know that people can develop some tolerance to cannabis across time, and so it makes sense that their dose would escalate a little bit across time. We found that changes in migraine severity ratings did not change across time. So, we found that cannabis was equally effective in reducing migraine across time. But people, again, are using larger doses to basically achieve the exact same benefits of cannabis on migraine over time. More concerningly with headache in that we found that people were using larger doses across time, but they were reporting that the cannabis was less effective across time. So we were seeing smaller reductions in headache across time, despite the increase in dose, which suggests, again, that people might be developing a little bit of tolerance to these effects.

Kirk: Okay, fair comment. I've hit all my points. Is there anything part of the study that you would like our listeners to know that I didn't touch on?

Dr. Cuttler: Yes, so the one thing that we did find that was more positive after finding these this evidence for tolerance was we did not see evidence for medication overuse headache. So, a lot of more conventional medications can produce medication overuse headaches, which are basically that people start to have headaches more frequently and have more severe headache over time as they continue to use their medications. And we did not find evidence for that. We looked at baseline headache and migraine severity ratings across time to see whether people's baseline ratings of these changed. And they did not. They remained static over time. And so, again, that would suggest that cannabis is not associated with the same medication overuse headache, that more conventional treatments are.

Kirk: Wonderful. Thank you. I'm going to pass you on to Trevor. He's got a couple of questions for you.

Dr. Cuttler: Sure.

Trevor: Hi, Dr. Cuttler, thank you very much for taking this. And I'm really glad you talked about the medication overuse as. Yeah, people forget about that. I remember one patient in particular. She was using NSAIDs suppositories after a C-section and we couldn't figure out why she suddenly developed these ridiculous headaches. And it was just she was getting too used to the NSAIDs suppositories. So, a couple things and we might not know why, but we touched on it briefly is there seem to be sex differences between male and female response. Do we have any idea why the males seem to get better, better relief than females from cannabis and migraines?

Dr. Cuttler: No. Unfortunately, we don't. And we predicted the opposite. We thought females would report greater relief and then we found that males reported greater relief. So that's very difficult to explain. I believe that the males had higher baseline ratings to begin with, which means they had more room to go down. Does that make sense?  That they were rating their headaches worse at baseline and so potentially just had more room to come down. But we don't really understand that sex difference and it would need to be probed using more systematic research.

Trevor: Oh, thank you. And the other is now I know this one's a little unfair, too, but we know this isn't a double blind, placebo controlled trial. But, since it didn't seem to matter, the dose the people were on, whether doing how much THC, how much CBD, flower, concentrate; everyone got better. Any chance this is just a placebo effect that you know?

Dr. Cuttler: Absolutely.

Trevor: That people just, you know, they're like smoking cannabis and so they feel better.

Dr. Cuttler: Absolutely. There is that possibility. And that's the primary limitation to this research method, is that we are not able to institute a placebo control group. We do know that about roughly 30% of people seem to report placebo effect. We were seeing more like 90% of patients reporting effects of cannabis. But it's also important to remember that this is a self-selected group of individuals who are clearly using cannabis repeatedly to manage their headache and migraine. Otherwise they wouldn't be using Strainprint. So, we absolutely believe that our study is overestimating the effect, but it does demonstrate the potential beneficial effects in people who are using for this purpose. Again, I don't think that it's purely the placebo effect. I once again, as I was saying earlier, I believe that part of the effects of cannabis on headache and migraine are in reducing some of the emotional distress, which really does seem to exacerbate the pain. But definitely there is going to be some placebo effect at play here. I also don't worry so much about the placebo effect because the placebo effect is at play in everyday life. It's always in play in real life. And so when people are using cannabis to manage their headache and migraine, they have expectations about what the effects of this drug are going to be. And so the placebo effect is a natural effect of any drug, including cannabis.

Trevor: Oh, no, I completely agree. And before our listeners, you know, jump all over me on Twitter, I'm not against it. But I'm just thinking, like as a pharmacist, people ask, you know, oh, does this drug work better at this strength? Does this drug so, you know, people ask all the time, you know, should we have this Terpene rather than that Terpene? Should we have high THC. Should be have low THC? Should, you know, should be a flower, should it be a concentrate? And if they all seem to work now, maybe Kirk's right and, you know, maybe this is just an example, the entourage effect or maybe it's a placebo or maybe just need further study. I'm just I thought it was really interesting that it didn't route and dose and didn't all didn't seem to matter very much.

Dr. Cuttler: Yes, and I agree, and I was somewhat surprised by that and I agree that that makes the placebo effect more suspect. It also, as I indicated, could just indicate that the THC, CBD and dose information is not super reliable. If we just have a lot of unreliable reports there and unreliable test results there from, you know, THC and CBD analysis, which we know those are not super reliable tests, then that could also produce nil results. And so it's not necessarily to say that dose doesn't matter, THC, CBD don't matter. We don't we don't find evidence that they do matter. It doesn't mean they don't matter because again, it could just be that the information, the data that we were analyzing on those specific variables was not very reliable. And so, what we're hoping is that this study will help to instigate more rigorous, placebo controlled trials of whole plant cannabis, where they do proper variation of THC, CBD and dose in a much more controlled manner. Where the experimenters are controlling the amount of THC people get and the dose that people get rather than individuals self-titrating and choosing their own cannabis. So, my study has the benefits of very strong what we call external or ecological validity in that my study really maps onto what users might experience in the real world using their own cannabis at their own doses. But it suffers from problems with what we call internal validity, which is our ability to say that cannabis and only cannabis is producing these changes. We know that the changes might also be due to things like the placebo effect and people's expectations. We know that we're looking at a self-selected group of people who repeatedly are using cannabis to manage headache and migraine. Clearly, somebody who finds that it's completely ineffective for these purposes is not going to be using the app regularly. And so they would be underrepresented in this data set.

Trevor: Well, thank you. That is fantastic. I'm done, Kirk apparently has one more question before we let you go. Thank you for your patience.

Kirk: A little tag teaming here in the in the beginning of this conversation, you had said that you have done other studies with cannabis. Does this study relate and correlate with the studies you've done before? Because you said before that you did have you did have the ability to have two groups, you were able to study two groups that are cannabis and non-cannabis. Did the results of this study…

Dr. Cuttler: So that was looking at sober users and non-users. So I basically differentiate my studies as acute studies like this one where we're looking at the acute intoxicating effects of cannabis. I've done other I did another Strainprint study and it was published in the Journal of Affective Disorder is where we looked at the effects of cannabis on depression, anxiety and stress and using Strainprint data as well. The study I was referring to where we put people through a stress manipulation and measured their cortisol and subjective stress ratings with actually what I refer to as a chronic study in that I was looking at people who use cannabis on a daily or near daily basis and comparing them to people who don't use cannabis at all when everybody was entirely sober.

Kirk: And did the results come out about the same, that cannabis does have an effect, obviously?

Dr. Cuttler: Well, what we've we are what we found with this Strainprint study, looking at the acute effects of cannabis on stress was that people self-reported that cannabis reduced their perceived stress by about 60 percent. And what we found in the laboratory study, looking at the chronic effects of cannabis on the actual stress response, where we put people through an objective stressor was that people's stress response was blunted, that they reported that the stressor didn't was not as stressful, basically as non-users found it. And their hormonal response also demonstrated that they did not find the stressor as stressful as the nonusers did.

Kirk: OK, this is also fascinating Dr. Cuttler, I truly thank you for this. Thank you. Have a great day.

Kirk: So that was interesting.  I really enjoyed, I got a smile out of the fact when she said that when she when she came forward and said, you know, we about the placebo effect and, you know, I was thinking, you know, when you see someone smoking a reefer or, you know, smoking a flower, what's the first thing you usually see that people recreational user, I don't want to use the word stoners, but the first thing that you see in a recreational user of what's the first thing they would do?

Trevor: Sit down, reach for a bag of Cheetos.

Kirk: Stereotype.

Trevor: Yeah, but.

Kirk: But one of the first things they do is just go, just a deep sigh when they allow that effect of cannabis to come into your body.  So, I can't help but wonder if maybe just stoners, I'm going to say the word stoners just are mellow people.

Trevor: Well, no. And I thought it was she said, you know, completely her thoughts. You can't back it up. But I really thought it was interesting, her thought that maybe cannabis doesn't directly, quote unquote, affect pain. Like, you know, opioids, we know reduces pain by working out the opioid receptors. Maybe it is a affect your mood, which sounds a little wishy washy, but if you follow her logic, it makes sense that if you aren't worried about the pain in your toe, you've got less pain in your toe.

Kirk: But we've observed it. I mean, we've observed the circle. When you're sitting in a circle in the back of a back alley of a bar and someone's passing your reefer, I mean, we've seen people instantly relax. So there is an effect, the psychological effect on it. But what do you think about the whole, you know, CBD have anti-inflammatory effects. So, you know, the throbbing I mean, how are headaches? How are headaches? They're seeing and here that it might be a decreased level of anandamide but also is or not effect of heart rate and maybe inflammation in the brain in the vessels. Aren't headaches caused by a little bit inflammation. what causes headaches?

Trevor: It seems every time I go to a migraine CU talk it something different. But yeah, definitely 20 years ago we said it was, you know, pulsating in and blood vessels in the brain. I don't know if that's what we currently think of migraine is; seems to be evolving. But she touched on something very the beginning that we've run into a couple more times now, which keeps surprising me. I'd like to talk to more people about it.  Is somebody who has migraines, apparently a few other conditions actually endocannabinoid deficient.

Kirk: Right.

Trevor: And if that's really a thing and you know, I'm not saying it is and I'm just saying this is semi-new to me. Then go, wow, if they're endocannabinoid deficient, you know, the best way to treat them is to give them cannabinoids.

Kirk: Well, maybe this is an opportunity for our listeners who suffer from headaches is to go to your GP and say, hey, how about testing my endocannabinoid system and seeing if I'm deficient?

Trevor: I don't know if there's a good way to do that,.

Kirk: But there must be. I mean, there must be a way of measuring your anandamide.

Trevor: Well, probably in like a university lab, but your average GP, I don't think has access to that. Probably the best substitute is try cannabis and see what happens. No, I just I'm just throwing that out there.

Kirk: Are we canna-positive here.

Trevor: We might be canna-positive, but it just it's interesting. And we're going to I'm looking forward to exploring more about actual endocannabinoid deficiencies in different. If this is a real thing and what it all else that affects.

Kirk: What I like about this study is that it says right up front, or buried into there. Wherever you look at it, because of this study, they are looking for somebody to collaborate it. This is a new study. It has not been collaborated with other studies. They recognize that in the paper. However, they are also saying there is definitely effects. Cannabis does have an effect. And that's what I like about this paper.  Again, it reinforces what we said in one of our very first episodes. We need more research. And I'm surprised as a Canadian researcher of cannabis, she hasn't found a position in Canada. I that's odd.

Trevor: Yeah, that's via the Twitter verse. Nope. This was a really good one. And again, we keep saying we want more research. So, here's a good example of where a Strainprint research is helping people.

Kirk: What I would like to do next is I'm going to be searching for a prescriber, somebody that actually prescribes for cannabis and migraines. So, look out for a future episode on that. All right. Reefer Medness - The podcast.

Trevor: It's been another good one.

Kirk: Been another good one. And we'll just bend our producers ear Parkland poet. Renee will come up with some music from the CDKM studios here in Dauphin, Manitoba, Canada.

Trevor: City of Sunshine.

Kirk: City of Sunshine.

Rene: Only about an hour or so away from the city of Sunshine Dauphin, Manitoba. Right here in the Parkland region is a place called Roblin and a guy named Jimmy Z went to college there. Great blues guy. So, the musical picked for today, staying close to the Dauphin area. Certainly, within the Parkland. I've chosen a song called I Ride Alone by The Jimmy Z Band.

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